Research Area

Research Interests

Dr. Allan’s research interests lie in the study of molecular mechanisms that influence normal cellular growth, tumor development, and cancer progression. The focus of Dr. Allan’s research program is cancer metastasis and translational research. Despite the fact that the majority of deaths from solid cancer occur due to the physiological effects of metastasis rather than from the consequences of the primary tumor, metastasis remains a badly understudied field. A major area of research that is needed to address this problem involves gaining a greater understanding of the metastatic process as a whole, such that current therapies can be better utilized to target metastatic disease, and new, more effective therapies can be developed which will better treat or prevent cancer metastasis. A second important area of research is the identification and development of surrogate marker approaches that will allow close monitoring of both disease progression and response to therapy. Dr. Allan’s research program encompasses both of these areas, and involves two individual but interrelated projects.

Current Projects

Clinical studies have shown that rare disseminated tumor cells in the peripheral bloodstream or bone marrow of patients with breast and other cancers may be an important indicator of the potential for metastatic disease and poor prognosis. However, the biological implications of these cells remain poorly understood, particularly with regards to the functional and mechanistic details of their progression to clinically relevant metastases. Our lab has established novel and sensitive methods to identify and characterize rare disseminated tumor cells in the blood, bone marrow, and distant organ sites in mouse models of human breast cancer, as well as in the peripheral blood of cancer patients. These studies are helping us elucidate the mechanistic details of early steps in metastasis and how these steps relate to the development of life-threatening metastases in animal models and patients. In addition, these methods will be extremely valuable for the future identification, development, and testing of new therapeutic strategies to combat breast and other cancers.

2. Role of cancer stem cells in breast cancer metastasis and treatment:

Metastasis is an inefficient process, such that very few cells that leave a tumor successfully form macrometastases in distant sites. This, coupled with the inherently heterogeneous nature of the cancer cell population within solid tumors, suggests that only a small subpopulation of cells can successfully initiate tumor growth and navigate the metastatic cascade to eventually form life-threatening metastases in distant organs. We hypothesize that this rare subpopulation of cells are in fact cancer stem cells (CSCs). Recent experimental studies in our lab indicate that breast cancer cells with a "stem-like" phenotype display enhanced adhesion, migration, invasion, metastasis, and therapy resistance. In collaboration with the LHSC Divisions of Surgery, Oncology, and Hematology, our lab has also undertaken translational studies aimed at characterizing breast cancer CSCs in patient samples, including assessment of the role that CSCs play in patient response to chemotherapy and radiation treatment. Taken together, these novel studies will allow us to answer a number of important and previously uninvestigated questions regarding the role of CSCs in breast cancer metastasis and treatment. Although some early stage cancers can be successfully treated by surgery, radiation, and/or chemotherapy, the majority of current therapies fail in the metastatic setting. Therefore, our consideration of the CSC hypothesis in the context of metastasis and response to therapy could have far-reaching implications to the way that we not only study cancer, but more importantly how we treat it.

Key Collaborators

Anargyros Xenocostas, MD, FRCPC
Hematology, London Health Sciences Centre; and Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario

Tracy Sexton, MD, PhD, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology and Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario

Michael Lock, MD, CCFP, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Department of Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario

Muriel Brackstone, MSc, MD, FRCPC
Surgical Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Surgery and Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario

Ann F. Chambers, Ph.D.
Cancer Research, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology, Medical Biophysics, Pathology, and Microbiology & Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario

Jeremy Squire, Ph.D.

Department of Pathology and Molecular Medicine, Kingston General Hospital and Queen’s University; and National Cancer Institute of Canada Clinical Trials Group